RESUMO
A series of novel piperazine analogues bearing quinolin-8-yloxy-butan--ones/pyridin-2-yloxy-ethanones were synthesized by a simple and convenient approach based on various substituted piperazine incorporating quinoline and pyridine moieties. The analogues were evaluated for in vitro antioxidant activity against 2,2-diphenyl-1-picryl-hydrazyl (DPPH) and ferrous ion radical scavenging activities and anti-inflammatory activity by inhibition of Vipera russelli venom (PLA2) and gastric K+/H(+)-ATPase activities. Most of the title compounds exhibited promising activity. Best antioxidant and PLA2-inhibiting activities were found for piperazine analogues with phenyl and nitro phenyl groups, whereas methoxy group on phenyl piperazine indicated selectivity for the H+/K(+)-ATPase.
Assuntos
Anti-Inflamatórios/síntese química , Antioxidantes/síntese química , Inibidores Enzimáticos/síntese química , Piperazinas/síntese química , Piridinas/química , Quinolinas/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Compostos de Bifenilo/química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Radicais Livres/química , Fosfolipases A2 do Grupo II/antagonistas & inibidores , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Estrutura Molecular , Células Parietais Gástricas/efeitos dos fármacos , Células Parietais Gástricas/enzimologia , Picratos/química , Piperazinas/química , Piperazinas/farmacologia , OvinosRESUMO
One of the main strategies to inhibit the tumor growth is to promote the biochemical events leading to DNA degradation, which would eventually culminate in apoptosis. We have earlier reported that the 2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazole(DAO-9) possessed anti-cancer activity. To address the exact molecular mechanism underlying anti-cancer property, present study focused on evaluating the anti-tumor effect of the DAO-9 on murine ascites carcinoma cells using various in vivo and in vitro assays. The in vivo assays implicated a strong regression in tumor growth of ascites carcinoma after treatment which is due to apoptogenic efficacy as assessed through structural morphology of EAC cells by Giemsa, Acridine orange, Annexin V staining and FACS analysis. Nucleosomal DNA fragmentation induced by DAO-9 is due to activation of caspase-3 mediated DNAse as verified by endonuclease assays and immunoblot analysis. The caspase-3 activation mechanism is by induction of intrinsic cascade signaling molecules, such as p53, Bax, Bad and cytochrome c (cyt c) expression as verified by western blot. The results concluded that the tumor inhibiting activity of DAO-9 is due to activation of the apoptotic signaling cascade, which could be translated into targeted anti-cancer drug in the near future.
Assuntos
Apoptose/efeitos dos fármacos , Carcinoma de Ehrlich/enzimologia , Caspase 3/metabolismo , Endonucleases/metabolismo , Oxidiazóis/uso terapêutico , Proteína Supressora de Tumor p53/biossíntese , Animais , Apoptose/fisiologia , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/patologia , Ativação Enzimática , Feminino , Camundongos , Oxidiazóis/química , Oxidiazóis/farmacologiaRESUMO
In the title compound, C14H11FO2, the dihedral angles beteen the central C3O ketone residue and the fluoro- and hy-droxy-substituted benzene rings are 50.44â (9) and 12.63â (10)°, respectively. The planes of the benzene rings subtend a dihedral angle of 58.88â (9)° and an intra-molecular O-Hâ¯O hydrogen bond closes an S(6) ring. No directional inter-actions beyond van der Waals packing contacts were identified in the crystal structure.
RESUMO
In the title compound, C14H11FO2, the two benzene rings are not coplanar, with a dihedral angle of 57.45â (12)° between their planes. In the crystal, mol-ecules are linked by an O-Hâ¯O hydrogen bond, forming a 21 helical chain along the b axis.
RESUMO
In the mol-ecule of the title compound, C15H14O2, the dihedral angle between the benzene and phenyl rings is 61.27â (8)°. In the crystal, O-Hâ¯O and weak C-Hâ¯O hydrogen bonds link the mol-ecules into chains extending along the c-axis direction.
RESUMO
Reaction of 6a-f individually with 2-methylsulfonyl-4,6-dimethoxypyrimidine yielded 7a-f in excellent yield. The newly synthesized heterocycles were characterized by IR, (1)H NMR, and mass spectral data. Compounds 7a-f was screened for their anti-inflammatory activity and were compared with standard drugs. Of the compounds studied, the compound 7e showed more potent activity than the standard drugs at all doses tested.
Assuntos
Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/farmacologia , Pirimidinas/síntese química , Pirimidinas/farmacologia , Algoritmos , Animais , Animais Endogâmicos , Anti-Inflamatórios não Esteroides/química , Modelos Animais de Doenças , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/prevenção & controle , Pé/patologia , Camundongos , Fosfolipases A2/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Pirimidinas/química , Ratos , Úlcera/etiologiaRESUMO
Fries rearrangement of substituted phenyl benzoates 1a-j to substituted hydroxy benzophenones 2a-j was achieved in excellent yield. Further benzoylation of 2a-j to benzoyloxy benzophenones 4a-n, a benzophenone analogue was achieved in good yield. All the newly synthesized compounds were evaluated for their anti-inflammatory activity and were compared with standard drugs. Out of the compounds studied, the compounds 4c, 4e, 4g, 4h and 4k with chloro and methyl substituents at para position showed more potent activity than the standard drugs at all doses tested.
